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SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study.

ABSTRACT: The genetic variations among individuals are one of the notable factors determining disease severity and drug response. Nowadays, COVID-19 pandemic has been adversely affecting many aspects of human life. We used the Tehran Cardio-Metabolic Genetic Study (TCGS) data that is an ongoing genetic study including the whole-genome sequencing of 1200 individuals and chip genotyping of more than 15,000 participants. Here, the effect of ACE2 variations by focusing on the receptor-binding site of SARS-CoV-2 and ACE2 cleavage by TMPRSS2 protease were investigated through simulations study. After analyzing TCGS data, 570 genetic variations on the ACE2 gene, including single nucleotide polymorphisms (SNP) and insertion/deletion (INDEL) were detected. Interestingly, two observed missense variants, K26R and S331F, which only the first one was previously reported, can reduce the receptor affinity for the viral Spike protein. Moreover, our bioinformatics simulation of 3D structures and docking of proteins explains important details of ACE2-Spike and ACE2-TMPRSS2 interactions, especially the critical role of Arg652 of ACE2 for protease function of TMPRSS2 was uncovered. As our results show that the genetic variation of ACE2 can at least influence the affinity of this receptor to its partners, we need to consider the genetic variations on ACE2 as well as other genes in the pathways that contribute to the pathogenesis of COVID-19 for designing efficient drugs and vaccines.

SUBMITTER: Lanjanian H

PROVIDER: S-EPMC7810897 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study.

Lanjanian Hossein H Moazzam-Jazi Maryam M Hedayati Mehdi M Akbarzadeh Mahdi M Guity Kamran K Sedaghati-Khayat Bahareh B Azizi Fereidoun F Daneshpour Maryam S MS

Scientific reports 20210115 1

The genetic variations among individuals are one of the notable factors determining disease severity and drug response. Nowadays, COVID-19 pandemic has been adversely affecting many aspects of human life. We used the Tehran Cardio-Metabolic Genetic Study (TCGS) data that is an ongoing genetic study including the whole-genome sequencing of 1200 individuals and chip genotyping of more than 15,000 participants. Here, the effect of ACE2 variations by focusing on the receptor-binding site of SARS-CoV ...[more]

PMID: 33452303

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Project description:BackgroundNon-participation in cohort studies, if associated with both the exposure and occurrence of the event, can introduce bias in the estimates of interest. This study aims to identify factors associated with follow-up participation in Tehran Lipid and Glucose Study, a large-scale community-based prospective study in West Asia.MethodsA sample of 10,368 adults from TLGS was included in the analysis. All analyses were split according to sex and age groups (20-39, 40-59, and 60 years). The associations between socio-demographic, health, and lifestyle factors with response rate were identified using the Generalized Estimating Equations model.ResultsOver the median of 15.7 years of follow up the response rate was 64.5%. The highest response rate was observed in those aged 40-59 years for both sexes. Current smokers had lower odds of response in both sexes for all age groups, ranging from 0.51 to 0.74, p < 0.01. In young adults, being single (OR = 0.79, OR = 0.57, p ≤ 0.01, respectively for men and women) and unemployed (OR = 0.73, OR = 0.76, p ≤ 0.01, respectively for men and women) in both sexes, high physical activity in men (OR = 0.77, p < 0.01), high education (OR = 0.75, p = 0.02) and obesity (OR = 0.85, p = 0.05) in women were associated with lower response rate. For the middle-aged group, diabetes in men (OR = 0.77, p = 0.05) and hypertension (OR = 0.84, p = 0.05), and having a history of cancer (OR = 0.43, p = 0.03) in women were factors associated with lower response rates. Finally, interventions for both sexes (OR = 0.75, OR = 0.77, p ≤ 0.05, respectively for men and women) and being divorced/widow in women (OR = 0.77, p = 0.05) were the factors associated with the lower response rate in the elderly.ConclusionsLong-term participation was influenced by socio-demographic, health, and lifestyle factors in different sex- and age-specific patterns in TLGS. Recruitment strategies targeting these factors may improve participant follow-up in longitudinal studies.

Dataset Information

SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study.

Publications

SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study.

Similar Datasets

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